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Cold Spring Harbor Perspectives in... Mar 2018Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesions and their relation to the inflammatory process is described. Pathology suggests that inflammation drives tissue injury at all stages of the disease. Focal inflammatory infiltrates in the meninges and the perivascular spaces appear to produce soluble factors, which induce demyelination or neurodegeneration either directly or indirectly through microglia activation. The nature of these soluble factors, which are responsible for demyelinating activity in sera and cerebrospinal fluid of the patients, is currently undefined. Demyelination and neurodegeneration is finally accomplished by oxidative injury and mitochondrial damage leading to a state of "virtual hypoxia."
Topics: Brain; Demyelinating Diseases; Disease Progression; Humans; Inflammation; Multiple Sclerosis; Nerve Degeneration
PubMed: 29358320
DOI: 10.1101/cshperspect.a028936 -
Neurologia 2020Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no... (Review)
Review
INTRODUCTION
Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary.
DEVELOPMENT
We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models.
CONCLUSIONS
Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study.
Topics: Animals; Cuprizone; Demyelinating Diseases; Humans; In Vitro Techniques; Multiple Sclerosis; Myelin Sheath; Remyelination
PubMed: 28863829
DOI: 10.1016/j.nrl.2017.07.002 -
Frontiers in Immunology 2020Microglia originate from myeloid progenitors in the embryonic yolk sac and play an integral role in central nervous system (CNS) development, immune surveillance and... (Review)
Review
Microglia originate from myeloid progenitors in the embryonic yolk sac and play an integral role in central nervous system (CNS) development, immune surveillance and repair. The role of microglia in multiple sclerosis (MS) has been complex and controversial, with evidence suggesting that these cells play key roles in both active inflammation and remyelination. Here we will review the most recent histological classification of MS lesions as well as the evidence supporting both inflammatory and reparative functions of these cells. We will also review how microglia may yield new biomarkers for MS activity and serve as a potential target for therapy.
Topics: Antirheumatic Agents; Biomarkers; Demyelinating Diseases; Genetic Diseases, Inborn; Humans; Immunologic Surveillance; Macrophages; Microglia; Multiple Sclerosis; Neurodegenerative Diseases; Neuroimaging; T-Lymphocyte Subsets
PubMed: 32265902
DOI: 10.3389/fimmu.2020.00374 -
The Lancet. Neurology Nov 2023Individuals can be deemed to have radiologically isolated syndrome (RIS) if they have incidental demyelinating-appearing lesions in their brain or spinal cord that are... (Review)
Review
Individuals can be deemed to have radiologically isolated syndrome (RIS) if they have incidental demyelinating-appearing lesions in their brain or spinal cord that are highly suggestive of multiple sclerosis but their clinical history does not include symptoms consistent with multiple sclerosis. Data from international longitudinal cohorts indicate that around half of people with RIS will develop relapsing or progressive symptoms of multiple sclerosis within 10 years, suggesting that in some individuals, RIS is a presymptomatic stage of multiple sclerosis. Risk factors for progression from RIS to clinical multiple sclerosis include younger age (ie, <35 years), male sex, CSF-restricted oligoclonal bands, spinal cord or infratentorial lesions, and gadolinium-enhancing lesions. Other imaging, biological, genetic, and digital biomarkers that might be of value in identifying individuals who are at the highest risk of developing multiple sclerosis need further investigation. Two 2-year randomised clinical trials showed the efficacy of approved multiple sclerosis immunomodulatory medications in preventing the clinical conversion to multiple sclerosis in some individuals with RIS. If substantiated in longer-term studies, these data have the potential to transform our approach to care for the people with RIS who are at the greatest risk of diagnosis with multiple sclerosis.
Topics: Humans; Male; Adult; Magnetic Resonance Imaging; Disease Progression; Demyelinating Diseases; Multiple Sclerosis; Spinal Cord
PubMed: 37839432
DOI: 10.1016/S1474-4422(23)00281-8 -
Handbook of Clinical Neurology 2017Inflammatory demyelinating diseases are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. The... (Review)
Review
Inflammatory demyelinating diseases are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. The pathologic hallmark of multiple sclerosis (MS) is the presence of focal demyelinated lesions with partial axonal preservation and reactive astrogliosis. Demyelinated plaques are present in the white as well as gray matter, such as the cerebral or cerebellar cortex and brainstem nuclei. Activity of the disease process is reflected by the presence of lesions with ongoing myelin destruction. Axonal and neuronal destruction in the lesions is a major substrate for permanent neurologic deficit in MS patients. The MS pathology is qualitatively similar in different disease stages, such as relapsing remitting MS or secondary or primary progressive MS, but the prevalence of different lesion types differs quantitatively. Acute MS and Balo's type of concentric sclerosis appear to be variants of classic MS. In contrast, neuromyelitis optica (NMO) and spectrum disorders (NMOSD) are inflammatory diseases with primary injury of astrocytes, mediated by aquaporin-4 antibodies. Finally, we discuss the histopathology of other inflammatory demyelinating diseases such as acute disseminated encephalomyelitis and myelin oligodendrocyte glycoprotein antibody-associated demyelination. Knowledge of the heterogenous immunopathology in demyelinating diseases is important, to understand the clinical presentation and disease course and to find the optimal treatment for an individual patient.
Topics: Animals; Central Nervous System; Demyelinating Diseases; Humans
PubMed: 28987175
DOI: 10.1016/B978-0-12-802395-2.00019-5 -
Neurologia I Neurochirurgia Polska 2020Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms of MS can appear in children and adolescents before the age of 18, and we call this paediatric MS (PMS). It is estimated that paediatric MS accounts for 3-5% of the general population of patients with MS. Despite the fundamental si-milarities to adult MS, PMS has many distinctive features. Paediatric MS has a milder course compared to adults, but leads to sig-nificant disability at an early age. PMS is relapsing-remitting in 95-98% of cases; the primary progressive manifestation is much less common than in adults. The differential diagnosis of MS in children should include other childhood demyelinating diseases, mitochondrial and metabolic diseases, connective tissue diseases, and neuroborreliosis. Differentiating acute disseminated en-cephalomyelitis (ADEM) from the first onset of MS remains the biggest challenge. Over the past 10 years, understanding of the epidemiology, pathophysiology, diagnosis, and treatment of MS in children has significantly expanded. The diagnostic criteria leading to earlier diagnosis and initiation of disease-modifying therapy (DMT) have changed, and the number of drugs used in children has increased. However, many important issues require further research. This review discusses the current state of knowledge regarding the epidemiology, diagnosis, and treatment of multiple sclerosis in children.
Topics: Adolescent; Adult; Central Nervous System; Child; Diagnosis, Differential; Humans; Multiple Sclerosis
PubMed: 32940341
DOI: 10.5603/PJNNS.a2020.0069 -
Semergen Sep 2015Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although... (Review)
Review
Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although there are several hypotheses, such as infections or genetics. In its pathophysiology, it seems that immune activation attacks the myelin sheath, causing a progressive and irreversible axonal degeneration. The disease produces a variety of symptoms, and diagnosis requires fulfilling a number of criteria and the exclusion of other possible causes. The role of neuroimaging is very important, especially Magnetic Resonance Imaging. Despite the availability of disease-modifying drugs, none of them are able to halt its progress, and the most useful drugs are those designed to alleviate the symptoms of outbreaks. Overall, multiple sclerosis requires a significant effort in research to clarify not only why and how it occurs, as well as the development of new measures to improve quality of life of affected patients.
Topics: Disease Progression; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Quality of Life
PubMed: 25442466
DOI: 10.1016/j.semerg.2014.07.011 -
The Lancet. Neurology Feb 2021The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological... (Review)
Review
The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological insights provided by advanced neuroimaging techniques, and high-level evidence for the therapeutic efficacy of biological agents are redefining diagnosis and care. Three distinct neuroimmune conditions-multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD)-can now be distinguished, with evidence from humans and animal models supporting distinct pathobiological disease mechanisms. The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children. However, doing clinical trials is challenging because of the rarity of these conditions in the paediatric age group, necessitating new approaches to trial design, including age-based trajectory modelling based on phase 3 studies in adults. Despite these limitations, the future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past, and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated.
Topics: Adolescent; Child; Demyelinating Diseases; Humans; Multiple Sclerosis; Neuroimaging; Young Adult
PubMed: 33484648
DOI: 10.1016/S1474-4422(20)30432-4 -
Seminars in Neurology Aug 2016Leukodystrophies are heritable disorders primarily affecting the white matter of the central nervous system. They are clinically characterized by spasticity, optic... (Review)
Review
Leukodystrophies are heritable disorders primarily affecting the white matter of the central nervous system. They are clinically characterized by spasticity, optic atrophy, and ataxia. These are a heterogeneous group of disorders, including hypomyelinating disorders and demyelinating disorders due to abnormal accumulations. Although individually rare, together they are responsible for substantial disease burden. Essentially all these disorders have infantile, juvenile, and adult presentations. Understanding the genetic and biochemical bases of these disorders opens the door to therapeutic approaches.
Topics: Adolescent; Adult; Ataxia; Brain Diseases; Child, Preschool; Demyelinating Diseases; Hereditary Central Nervous System Demyelinating Diseases; Humans; Infant; Lysosomal Storage Diseases
PubMed: 27643905
DOI: 10.1055/s-0036-1585455 -
Continuum (Minneapolis, Minn.) Oct 2017This article reviews the chronic demyelinating neuropathies, with a focus on the diagnosis and treatment of immune-mediated neuropathies and the features that can help... (Review)
Review
PURPOSE OF REVIEW
This article reviews the chronic demyelinating neuropathies, with a focus on the diagnosis and treatment of immune-mediated neuropathies and the features that can help differentiate immune-mediated neuropathies from other chronic demyelinating peripheral nerve conditions.
RECENT FINDINGS
Advances in clinical phenotyping and outcomes assessment have enabled neurologists to improve disease recognition, treatment, and disease monitoring. Our understanding of the immunopathogenesis of demyelinating neuropathies is evolving. Identification of new antibodies and recognition that node of Ranvier dysfunction may be an early pathogenic feature may herald further diagnostic and treatment advancements.
SUMMARY
The chronic demyelinating polyneuropathies are heterogeneous. The clinical and diagnostic features are sometimes overlapping, and the specific disorders are variable in pathogenesis, treatment, and prognosis. This heterogeneity underscores the importance of achieving diagnostic accuracy and implementing disease-specific treatment approaches.
Topics: Chronic Disease; Demyelinating Diseases; Humans; Polyneuropathies
PubMed: 28968364
DOI: 10.1212/CON.0000000000000517